Cytokine gene polymorphism might affect the outcome of clinical rejection in cardiac transplantation

D. Olga McDaniel, D. Perrin Roten, Sani Z. Yamout, Vernetta Coleman, Georgio Aru, Bobby Heath, Tammy S. Thomas, William W. Turner, Todd F. Chatham, Joseph A. Cameron, Charles K. Moore

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Introduction: Cardiac allograft rejection is associated with an individual's inflammatory cytokine gene polymorphism. It was hypothesized that possession of specific cytokine alleles might be influential in predisposing the recipient to allograft rejection. Methods: DNA from nucleated peripheral blood cells of 65 cardiac transplantation patients and 77 controls were tested for IL-2, TNF-α, TGF-β1, IL-10, IL-6, and IFN-γ gene polymorphism by polymerase chain reaction. Genotype variation was analyzed in view of the recipient's clinical condition and histopathological assessment for rejection. Transplant rejection was determined by endomyocardial biopsy and scored 1A, 2, and 3A/3B. Results: Overall, 57% of recipients at pre-transplantation suffered from ischemic-cardiomyopathy; whereas 43% had some form of non-ischemic- cardiomyopathy. There were fewer IL-10 high producer genotypes in recipients with 2 and 3A/3B rejection scores than in those with 1A scores (28.6% vs. 22.6% vs. 80%; P<0.01 respectively). IFN-γ low producer genotype was increased in African American recipients compared to white recipients with grade 3A/3B rejection (P<0.006, RR=2.4). A majority of recipients carried either the TGF-β1 TT/GG or TC/GG high producer genotype, but the ratio between the genotypes were reversibly associated with 3A/3B rejection grades in African Americans as compared with whites. Conclusions: The IL-10 high producer genotype appears to be an effective factor in protecting the recipients from rejection. The IFN-γ low producer genotype (A/A) was a greater risk factor for African American recipients as the intermediate producer genotype was for white recipients with 3A/3B rejections. Testing peripheral blood for genetic markers that controls the production levels of inflammatory cytokines might predict the outcome of allograft survival in cardiac transplant recipients.

Original languageEnglish (US)
Pages (from-to)68-80
Number of pages13
JournalJournal of Applied Research
Volume4
Issue number1
StatePublished - 2004

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Heart Transplantation
Genotype
Cytokines
Genes
African Americans
Interleukin-10
Allografts
Cardiomyopathies
Graft Rejection
Genetic Markers
Interleukin-2
Interleukin-6
Blood Cells
Transplantation
Alleles
Biopsy
Polymerase Chain Reaction
DNA

Keywords

  • Cytokine
  • Genotype
  • Polymorphism
  • Rejection
  • Transplantation

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology

Cite this

McDaniel, D. O., Roten, D. P., Yamout, S. Z., Coleman, V., Aru, G., Heath, B., ... Moore, C. K. (2004). Cytokine gene polymorphism might affect the outcome of clinical rejection in cardiac transplantation. Journal of Applied Research, 4(1), 68-80.

Cytokine gene polymorphism might affect the outcome of clinical rejection in cardiac transplantation. / McDaniel, D. Olga; Roten, D. Perrin; Yamout, Sani Z.; Coleman, Vernetta; Aru, Georgio; Heath, Bobby; Thomas, Tammy S.; Turner, William W.; Chatham, Todd F.; Cameron, Joseph A.; Moore, Charles K.

In: Journal of Applied Research, Vol. 4, No. 1, 2004, p. 68-80.

Research output: Contribution to journalArticle

McDaniel, DO, Roten, DP, Yamout, SZ, Coleman, V, Aru, G, Heath, B, Thomas, TS, Turner, WW, Chatham, TF, Cameron, JA & Moore, CK 2004, 'Cytokine gene polymorphism might affect the outcome of clinical rejection in cardiac transplantation', Journal of Applied Research, vol. 4, no. 1, pp. 68-80.
McDaniel DO, Roten DP, Yamout SZ, Coleman V, Aru G, Heath B et al. Cytokine gene polymorphism might affect the outcome of clinical rejection in cardiac transplantation. Journal of Applied Research. 2004;4(1):68-80.
McDaniel, D. Olga ; Roten, D. Perrin ; Yamout, Sani Z. ; Coleman, Vernetta ; Aru, Georgio ; Heath, Bobby ; Thomas, Tammy S. ; Turner, William W. ; Chatham, Todd F. ; Cameron, Joseph A. ; Moore, Charles K. / Cytokine gene polymorphism might affect the outcome of clinical rejection in cardiac transplantation. In: Journal of Applied Research. 2004 ; Vol. 4, No. 1. pp. 68-80.
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abstract = "Introduction: Cardiac allograft rejection is associated with an individual's inflammatory cytokine gene polymorphism. It was hypothesized that possession of specific cytokine alleles might be influential in predisposing the recipient to allograft rejection. Methods: DNA from nucleated peripheral blood cells of 65 cardiac transplantation patients and 77 controls were tested for IL-2, TNF-α, TGF-β1, IL-10, IL-6, and IFN-γ gene polymorphism by polymerase chain reaction. Genotype variation was analyzed in view of the recipient's clinical condition and histopathological assessment for rejection. Transplant rejection was determined by endomyocardial biopsy and scored 1A, 2, and 3A/3B. Results: Overall, 57{\%} of recipients at pre-transplantation suffered from ischemic-cardiomyopathy; whereas 43{\%} had some form of non-ischemic- cardiomyopathy. There were fewer IL-10 high producer genotypes in recipients with 2 and 3A/3B rejection scores than in those with 1A scores (28.6{\%} vs. 22.6{\%} vs. 80{\%}; P<0.01 respectively). IFN-γ low producer genotype was increased in African American recipients compared to white recipients with grade 3A/3B rejection (P<0.006, RR=2.4). A majority of recipients carried either the TGF-β1 TT/GG or TC/GG high producer genotype, but the ratio between the genotypes were reversibly associated with 3A/3B rejection grades in African Americans as compared with whites. Conclusions: The IL-10 high producer genotype appears to be an effective factor in protecting the recipients from rejection. The IFN-γ low producer genotype (A/A) was a greater risk factor for African American recipients as the intermediate producer genotype was for white recipients with 3A/3B rejections. Testing peripheral blood for genetic markers that controls the production levels of inflammatory cytokines might predict the outcome of allograft survival in cardiac transplant recipients.",
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T1 - Cytokine gene polymorphism might affect the outcome of clinical rejection in cardiac transplantation

AU - McDaniel, D. Olga

AU - Roten, D. Perrin

AU - Yamout, Sani Z.

AU - Coleman, Vernetta

AU - Aru, Georgio

AU - Heath, Bobby

AU - Thomas, Tammy S.

AU - Turner, William W.

AU - Chatham, Todd F.

AU - Cameron, Joseph A.

AU - Moore, Charles K.

PY - 2004

Y1 - 2004

N2 - Introduction: Cardiac allograft rejection is associated with an individual's inflammatory cytokine gene polymorphism. It was hypothesized that possession of specific cytokine alleles might be influential in predisposing the recipient to allograft rejection. Methods: DNA from nucleated peripheral blood cells of 65 cardiac transplantation patients and 77 controls were tested for IL-2, TNF-α, TGF-β1, IL-10, IL-6, and IFN-γ gene polymorphism by polymerase chain reaction. Genotype variation was analyzed in view of the recipient's clinical condition and histopathological assessment for rejection. Transplant rejection was determined by endomyocardial biopsy and scored 1A, 2, and 3A/3B. Results: Overall, 57% of recipients at pre-transplantation suffered from ischemic-cardiomyopathy; whereas 43% had some form of non-ischemic- cardiomyopathy. There were fewer IL-10 high producer genotypes in recipients with 2 and 3A/3B rejection scores than in those with 1A scores (28.6% vs. 22.6% vs. 80%; P<0.01 respectively). IFN-γ low producer genotype was increased in African American recipients compared to white recipients with grade 3A/3B rejection (P<0.006, RR=2.4). A majority of recipients carried either the TGF-β1 TT/GG or TC/GG high producer genotype, but the ratio between the genotypes were reversibly associated with 3A/3B rejection grades in African Americans as compared with whites. Conclusions: The IL-10 high producer genotype appears to be an effective factor in protecting the recipients from rejection. The IFN-γ low producer genotype (A/A) was a greater risk factor for African American recipients as the intermediate producer genotype was for white recipients with 3A/3B rejections. Testing peripheral blood for genetic markers that controls the production levels of inflammatory cytokines might predict the outcome of allograft survival in cardiac transplant recipients.

AB - Introduction: Cardiac allograft rejection is associated with an individual's inflammatory cytokine gene polymorphism. It was hypothesized that possession of specific cytokine alleles might be influential in predisposing the recipient to allograft rejection. Methods: DNA from nucleated peripheral blood cells of 65 cardiac transplantation patients and 77 controls were tested for IL-2, TNF-α, TGF-β1, IL-10, IL-6, and IFN-γ gene polymorphism by polymerase chain reaction. Genotype variation was analyzed in view of the recipient's clinical condition and histopathological assessment for rejection. Transplant rejection was determined by endomyocardial biopsy and scored 1A, 2, and 3A/3B. Results: Overall, 57% of recipients at pre-transplantation suffered from ischemic-cardiomyopathy; whereas 43% had some form of non-ischemic- cardiomyopathy. There were fewer IL-10 high producer genotypes in recipients with 2 and 3A/3B rejection scores than in those with 1A scores (28.6% vs. 22.6% vs. 80%; P<0.01 respectively). IFN-γ low producer genotype was increased in African American recipients compared to white recipients with grade 3A/3B rejection (P<0.006, RR=2.4). A majority of recipients carried either the TGF-β1 TT/GG or TC/GG high producer genotype, but the ratio between the genotypes were reversibly associated with 3A/3B rejection grades in African Americans as compared with whites. Conclusions: The IL-10 high producer genotype appears to be an effective factor in protecting the recipients from rejection. The IFN-γ low producer genotype (A/A) was a greater risk factor for African American recipients as the intermediate producer genotype was for white recipients with 3A/3B rejections. Testing peripheral blood for genetic markers that controls the production levels of inflammatory cytokines might predict the outcome of allograft survival in cardiac transplant recipients.

KW - Cytokine

KW - Genotype

KW - Polymorphism

KW - Rejection

KW - Transplantation

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